α-Melanocyte-stimulating hormone inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy / 中华实验眼科杂志

ABSTRACT

Background Retinal neovascularization (RNV) occurs in multiple eye diseases,which can lead to bleeding and retinal detachment.Therefore,inhibition of pathological RNV is becoming crucial to the treatment of ocular diseases.Research has shown that α-melanocyte-stimulating hormone (α-MSH) inhibits retinal angiogenesis during physiological development;however,the effects of α-MSH on pathological RNV remain unknown.Objective This study was to investigate the effects of intravitreal injection of α-MSH at different concentrations on pathological RNV in a mouse model of oxygen-induced retinopathy (OIR).Methods Forty healthy clean C57BL/6J mice were randomly divided into OIR+0.33 μg/μl α-MSH,OIR+ 1.67 μg/μl α-MSH,OIR+3.30 μg/μl α-MSH,OIR,and normal control groups at postnatal day 7 (P7),with 8 pups in each group.The α-MSH intervention groups and OIR group were exposed to high oxygen (75 ±2)％ for 5 days,then maintained under normal air condition for another 5 days;whereas the normal control group was raised under normoxia for 10 days.Retro-orbital injection of high molecular weight fluorescein isothiocyanate-dextran (FITC-dextran) was performed on P17 mice.The retina whole mounts were prepared to reveal retinal vasculature and quantify relative area of vessel obliteration.The mouse eyeballs were subjected to paraffin sections and hematoxylin-eosin staining,and the average number of pre-retinal nuclei per section was quantified.Results FITC-dextran labeled retinal whole mounts showed that the relative vessel obliteration area in normal control,OIR,OIR+0.33 μg/μl α-MSH,OIR+ 1.67 μg/μl α-MSH,and OIR+3.30 μg/μl α-MSH groups were (0.00±0.00) ％,(23.01 ±3.39) ％,(18.14±7.20) ％,(15.64±7.07) ％,and (7.62±6.52) ％,respectively.There was a statistical significance in the relative avascular area among the groups (F=19.635,P＜0.05).The relative avascular area in the OIR group was significantly higher than that in the OIR+3.30 μg/μl α-MSH group (t=4.293,P＜0.01).The results of histopathological examinations showed that the average number of pre-retinal nuclei per section in normal control,OIR,OIR+0.33 μg/μl α-MSH,OIR+1.67 μg/μl α-MSH,and OIR+3.30 μg/μl α-MSH groups were 0.00±0.00,11.45 ±4.26,6.35 ±2.34,4.96 ± 1.79 and 1.03 ± 1.25,respectively.There was a statistical significance in the average number of pre-retinal nuclei per section among the groups (F =147.87,P＜0.05).The average number of pre-retinal nuclei per section in the OIR group was significantly higher than that in the OIR+0.33 μg/μl α-MSH,OIR+ 1.67 μg/μl α-MSH,and OIR+3.30 μg/μl α-MSH groups,the differences between the groups had statistical significances (all at P＜0.001).Conclusions α-MSH reduces the relative area of vessel obliteration and the average number of pre-retinal nuclei in the retinas of OIR mouse model.The inhibitory effects of α-MSH on the pathological RNV are dose-dependent.